Abstract：
:Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction complex-independent manner, confirming that GMD is mechanistically distinct from nonsense-mediated mRNA decay (NMD). Efficient GMD requires PNRC2 (proline-rich nuclear receptor coregulatory protein 2) binding, helicase ability, and ATM-mediated phosphorylation of UPF1 (upstream frameshift 1). We also identify two GMD-specific factors: an RNA-binding protein, YBX1 (Y-box-binding protein 1), and an endoribonuclease, HRSP12 (heat-responsive protein 12). In particular, using HRSP12 variants, which are known to disrupt trimerization of HRSP12, we show that HRSP12 plays an essential role in the formation of a functionally active GMD complex. Moreover, we determine the hierarchical recruitment of GMD factors to target mRNAs. Finally, our genome-wide analysis shows that GMD targets a variety of transcripts, implicating roles in a wide range of cellular processes, including immune responses.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Park OH,Park J,Yu M,An HT,Ko J,Kim YKdoi
10.1101/gad.286484.116subject
Has Abstractpub_date
2016-09-15 00:00:00pages
2093-2105issue
18eissn
0890-9369issn
1549-5477pii
30/18/2093journal_volume
30pub_type
杂志文章abstract：:Pseudoplasmodia of developing Dictyostelium are organized with anteroposterior polarity. We have isolated CAR4, the gene for a new cell-surface, G protein-linked cAMP receptor. CAR4 mRNA is initially expressed during tip elongation and continues to accumulate into culmination. CAR4 is maximally expressed in pseudoplas...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.17.2086
更新日期：1994-09-01 00:00:00
abstract：:Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mous...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.258483.115
更新日期：2015-03-01 00:00:00
abstract：:Mismatch repair (MMR) has important roles in meiotic and mitotic recombination, DNA damage signaling, and various aspects of DNA metabolism including class-switch recombination, somatic hypermutation, and triplet-repeat expansion. Defects in MMR are responsible for human cancers characterized by microsatellite instabi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.430107
更新日期：2007-09-01 00:00:00
abstract：:The amino-terminal histone tails are subject to covalent post-translational modifications such as acetylation, methylation, and phosphorylation. In the histone code hypothesis, these exposed and unstructured histone tails are accessible to a repertoire of regulatory factors that specifically recognize the various modi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1001502
更新日期：2002-06-15 00:00:00
abstract：:The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant o...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1170904
更新日期：2004-03-15 00:00:00
abstract：:Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.2054311
更新日期：2011-05-15 00:00:00
abstract：:Cohesin is a chromosome-associated multisubunit protein complex that is highly conserved in eukaryotes and has close homologs in bacteria. Cohesin mediates cohesion between replicated sister chromatids and is therefore essential for chromosome segregation in dividing cells. Cohesin is also required for efficient repai...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.1724308
更新日期：2008-11-15 00:00:00
abstract：:Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subun...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.378206
更新日期：2006-06-01 00:00:00
abstract：:The acetylation state of histones plays a central role in determining gene expression in chromatin. The reestablishment of the acetylation state of nucleosomes after DNA replication and chromatin assembly requires both deacetylation and acetylation of specific lysine residues on newly incorporated histones. In this st...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.929001
更新日期：2001-12-01 00:00:00
abstract：:Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potent...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.226837.113
更新日期：2013-11-15 00:00:00
abstract：:Stem cells have been identified as a source of virtually all highly differentiated cells that are replenished during the lifetime of an animal. The critical balance between stem and differentiated cell populations is crucial for the long-term maintenance of functional tissue types. Stem cells maintain this balance by ...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.1602607
更新日期：2007-12-01 00:00:00
abstract：:The yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) coactivator complex exerts functions in gene expression, including activator interaction, histone acetylation, histone deubiquitination, mRNA export, chromatin recognition, and regulation of the basal transcription machinery. These diverse functions involve distinct modu...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.184705.111
更新日期：2012-03-15 00:00:00
abstract：:As in many polarized cells, spindle alignment in yeast is essential and cell cycle regulated. A key step that governs spindle alignment is the selective binding of the Kar9 protein to only one of the two spindle pole bodies (SPBs). It has been suggested that cyclin-dependent kinase Cdc28, in complex with cyclin Clb4, ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.298704
更新日期：2004-07-15 00:00:00
abstract：:In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.285460.116
更新日期：2016-07-01 00:00:00
abstract：:Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1823109
更新日期：2009-08-15 00:00:00
abstract：:In the metazoan germline, piwi proteins and associated piwi-interacting RNAs (piRNAs) provide a defense system against the expression of transposable elements. In the cytoplasm, piRNA sequences guide piwi complexes to destroy complementary transposon transcripts by endonucleolytic cleavage. However, some piwi family m...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.209841.112
更新日期：2013-02-15 00:00:00
abstract：:Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, re...
journal_title：Genes & development
pub_type： 杂志文章
doi：
更新日期：2000-07-15 00:00:00
abstract：:Medulloblastomas are brain tumors that arise in the cerebellum of children and contain stem cells in a perivascular niche thought to give rise to recurrence following radiation. We used several mouse models of medulloblastomas in parallel to better understand how the critical cell types in these tumors respond to ther...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1627008
更新日期：2008-02-15 00:00:00
abstract：:PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1323805
更新日期：2005-07-15 00:00:00
abstract：:Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a ne...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1221804
更新日期：2004-11-15 00:00:00
abstract：:Regulated cell expansion is an important determinant of organ shape in higher plants. The sabre mutation results in abnormal cell expansion in Arabidopsis. There is a shift in the orientation of expansion evident primarily in root cortex cells. The SABRE gene has been cloned and found to encode a novel protein. Reduct...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.3.330
更新日期：1995-02-01 00:00:00
abstract：:Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1482106
更新日期：2006-11-15 00:00:00
abstract：:Transcription of erythroid-expressed genes and normal erythroid development in vivo are dependent on a regulatory protein (GATA-1) that recognizes a consensus GATA motif. GATA-1 expression is itself restricted to erythroid progenitors and to two related hematopoietic lineages, megakaryocytes and mast cells. During cel...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.6.919
更新日期：1991-06-01 00:00:00
abstract：:The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits translation and generally commits the mRNA to irreversible 5'-to-3' exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by DCP1, and these proteins form the conserved core of the decapping complex. Additional decapping fact...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.227843.113
更新日期：2013-12-15 00:00:00
abstract：:The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required for organogenesis. Targeted deletion of the COUP-TFII gene results in embryonic lethality with defects in angiogenesis and heart development. COUP-TFII mutants are defecti...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.8.1037
更新日期：1999-04-15 00:00:00
abstract：:Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1825809
更新日期：2009-09-15 00:00:00
abstract：:Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.297135.117
更新日期：2017-05-15 00:00:00
abstract：:Hypoxia induces rapid and dramatic changes in cellular metabolism, in part through inhibition of target of rapamycin (TOR) kinase complex 1 (TORC1) activity. Genetic studies have shown the tuberous sclerosis tumor suppressors TSC1/2 and the REDD1 protein to be essential for hypoxia regulation of TORC1 activity in Dros...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1617608
更新日期：2008-01-15 00:00:00
abstract：:Extensive DNA elimination via a DNA breakage and rejoining process occurs during macronuclear development in the hypotrich ciliate Euplotes crassus. The excision process involves the removal of short, unique segments of DNA (internal eliminated sequences; IESs) and at least two highly repetitive families of transposon...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.7.1.84
更新日期：1993-01-01 00:00:00
abstract：:Pre-rRNA transcription by RNA Polymerase I (Pol I) is very robust on active rDNA repeats. Loss of yeast Topoisomerase I (Top1) generated truncated pre-rRNA fragments, which were stabilized in strains lacking TRAMP (Trf4/Trf5-Air1/Air2-Mtr4 polyadenylation complexes) or exosome degradation activities. Loss of both Top1...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.573310
更新日期：2010-07-15 00:00:00
